N-acetyltransferase 10 regulates chemokine expression in keratinocytes and promotes atopic dermatitis.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder with complex immunological underpinnings, yet the role of the RNA acetyltransferase NAT10 in its pathogenesis remains unclear. We investigated NAT10 function through cutaneous NAT10 knockdown (microneedle-delivered AAV-shRNA) and pharmacological inhibition (Remodelin), using 2,4-dinitrochlorobenzene- and ovalbumin-induced murine AD models combined with IFN-γ/TNF-α-stimulated HaCaT keratinocytes. Results showed elevated NAT10 expression and acetylcytidine modification in AD keratinocytes. NAT10 knockdown ameliorated skin pathology, reduced serum IgE, and selectively limited neutrophil infiltration by suppressing chemokines (CXCL8, CCL5, CXCL9, CXCL10, CCL2), whereas its overexpression promoted their expression. Mechanistically, NAT10 stabilized RELB mRNA via acetylcytidine modification, thereby activating NF-κB signaling. Remodelin suppressed keratinocyte chemokine production and neutrophil recruitment, improving skin lesions without toxicity. Collectively, NAT10 emerges as a central regulator of keratinocyte-driven inflammation and a viable therapeutic target in AD.